Multi-capillary optical detection system

ABSTRACT

An optical detection system for a capillary electrophoresis instrument is disclosed. The system includes an ultraviolet (UV) source and an absorption measurement optical path. In an embodiment, the optical path comprises a first plurality of optical elements arranged to obtain a plurality of respective UV beamlets from a UV beam emitted by the UV source and to direct the respective UV beamlets transversely through respective capillaries of a plurality of capillaries and to an absorption detector positioned to detect respective signals for use in obtaining respective UV absorption measurements corresponding to the respective capillaries.

FIELD OF THE DISCLOSURE

This disclosure relates generally to optical detection systems forcapillary electrophoresis instruments.

BACKGROUND

Existing capillary electrophoresis instruments analyze samples usingvisible light or other electromagnetic sources to excite and measurefluorescence of a sample-filled capillary. Certain other capillaryelectrophoresis instruments analyze samples using ultraviolet (UV)sources to measure absorption of UV radiation by a sample-filledcapillary.

SUMMARY

There is an increasing need for a high-throughput and high-qualitycapillary electrophoresis (CE) analysis platform. One way to efficientlyincrease throughput is by conducting measurements across a plurality ofcapillaries simultaneously. However, in the context of ultraviolet (UV)absorption measurements, prior methods have not achieved suchmeasurement efficiently. Some embodiments of the present inventionprovide a multi-capillary CE optical detection system that efficientlyprovides UV absorption measurements across a plurality of capillariesusing a single UV source. For certain types of samples, e.g., proteins,combining multiple types of electromagnetic measurements in a singlesystem would be especially useful. Some embodiments provide multipletypes of measurements in a single system. In one embodiment, opticalpaths allow use of a single UV source for both UV absorptionmeasurements and for exciting and measuring UV fluorescence. In anotherembodiment, optical paths allow using two different UV sources tomeasure UV absorption at different wavelengths. Some embodiments alsoinclude an optical path for using a visible light source to excite andmeasure fluorescence. In some embodiments, point sources are used and adigital signal processing unit utilizes signals from a referencecapillary to remove source and capillary noise from signalscorresponding to sample-filled capillaries. In some embodiments, thesystem is particularly applicable to measuring protein samples. In someembodiments, the system is applicable to other types of samples. Theseand other embodiments and variations thereof are more fully describedbelow.

Various other aspects of the inventive subject matter will become moreapparent from the following description, along with the accompanyingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a high-level diagram illustrating portions of a sampleseparation and identification instrument including an optical detectionsystem in accordance with one embodiment of the present invention.

FIG. 2 illustrates an embodiment of the optical detection system of theembodiment of FIG. 1.

FIG. 3 illustrates certain additional details regarding the embodimentof FIG. 2.

FIG. 4 illustrates certain additional details regarding the embodimentof FIG. 2.

FIG. 5 illustrates certain additional details regarding the embodimentof FIG. 2.

FIG. 6 illustrates certain additional details regarding the embodimentof FIG. 2.

FIG. 7 illustrates signals from the detectors shown in FIGS. 1-6 andinput to the digital signal processing unit shown in FIG. 1. FIG. 7 alsoillustrates signals output by the digital signal processing unit.

While the invention is described with reference to the above drawings,the drawings are intended to be illustrative, and other embodiments areconsistent with the spirit, and within the scope, of the invention.

DETAILED DESCRIPTION

The various embodiments now will be described more fully hereinafterwith reference to the accompanying drawings, which form a part hereof,and which show, by way of illustration, specific examples of practicingthe embodiments. This specification may, however, be embodied in manydifferent forms and should not be construed as limited to theembodiments set forth herein; rather, these embodiments are provided sothat this specification will be thorough and complete, and will fullyconvey the scope of the invention to those skilled in the art. Amongother things, this specification may be embodied as methods or devices.Accordingly, any of the various embodiments herein may take the form ofan entirely hardware embodiment, an entirely software embodiment or anembodiment combining software and hardware aspects. The followingspecification is, therefore, not to be taken in a limiting sense.

FIG. 1 is a high-level diagram illustrating portions of a sampleseparation and identification instrument 1000 including an opticaldetection system in accordance with one embodiment of the presentinvention. In the illustrated embodiment, instrument 1000 is a capillaryelectrophoresis (CE) instrument comprising at least one capillary 101having an outer capillary diameter and an inner capillary channeldiameter of a capillary channel through which a sample or other liquidmay flow.

With additional reference to FIG. 2, instrument 1000 comprises anoptical detection system 200 comprising sources 201, 202, and 203. Asused herein, unless otherwise indicated or implied, “source” refers to asource of electromagnetic radiation, for example, a source ofultra-violet (UV) radiation, visible light, near-infrared, and/orinfrared radiation. The terms “UV source” and “UV light source” will beused interchangeably herein to mean a source producing radiationprimarily or exclusively within UV band of the electromagnetic spectrum,e.g., from about 10 nanometers (“nm”) to 400 nm. As used herein the term“visible light source” means a source producing radiation primarily orexclusively within visible light band of the electromagnetic spectrum(e.g., from about 380 nm to 740 nm).

In the illustrated embodiment, source 201 comprises a first UV sourceproviding UV beam b1 having a first wavelength or wavelength band andsource 202 comprises a second UV source providing UV beam b2 having asecond wavelength or wavelength band. Source 203 may be a visible lightsource 203 providing visible light beam b3. In one embodiment, beam b1has a nominal or peak output at a wavelength that is at or near 220 nmand beam b2 has a nominal or peak output at a wavelength that is at ornear 280 nm. In alternative embodiments, these wavelengths might bedifferent without departing from the spirit and scope of the invention.In a preferred embodiment, UV sources 201 and 202 each comprise a UVlaser or similar UV source. In certain embodiments, sources 201 and 202may comprise a deuterium lamp, a UV light emitting diode (LED), or thelike.

In one embodiment, sources 201 and/or 202 may be configured to provide abeam that can be focused to provide a beam or spot at or near eachcapillary 101 having a diameter that is equal or approximately equal toan inner capillary diameter (e.g., a diameter twice the inner capillarydiameter), preferably a diameter at or near the capillary that is lessthan the inner capillary diameter. It has been found that transmittanceor absorption measurements can be made with better sensitivity with theuse of a smaller beam/spot diameter at or near the capillary because,for example, a higher percentage of the beam is impacted by variationsin transmittance or absorption of the sample, sample solution or othersubstance flowing through the inner capillary channel.

In a preferred embodiment, sources 201 and/or 202 are point sources. Asused herein, the term “point source” refers to a source that produces abeam that can be focused to a spot (cross-section or slice of the beamat a particular location) at or near a capillary having a beam diameterthat is less than or equal to the diameter of an inner channel of thecapillary. As used herein, in the case of a source producing a beamhaving, or characterized by, a Gaussian shape (e.g., a laser source),the term “beam diameter” means the 1/e² diameter of the beam at aparticular location along the beam's optical path (e.g., at capillary101). As used herein, in the case of a source producing a beam nothaving, or not characterized by, a Gaussian shape, the term “beamdiameter” means a diameter of the smallest circle or aperture containing85% of the energy or power in a cross-section of the beam at aparticular location in the beam's optical path (e.g., at a capillary101).

Source 203 comprises a visible light source providing visible light beamb3, for example, light having a nominal or peak output at a wavelengthat or near 505 nm or some other wavelength within the visible lightrange. In some embodiments, source 203 is a visible broadband lightsource or a white light source. In certain embodiments, source 203 andbeam b3 may further comprise at least some radiation in the UV and/orinfrared wavelength band ranges. Source 203 and beam b3 may comprise arange of wavelengths, for example, a wavelength range suitable forexciting a plurality of dyes excited at different wavelengths (e.g., awavelength range over all or part of the visible light wavelength rangeor a wavelength range also including radiation in the infrared and/orultraviolet wavelength band). In certain embodiments, source 203 maycomprise electromagnetic radiation in visible band, as well as in theultraviolet, infrared, and/or near-infrared with sufficient energy toexcite dyes sensitive to radiation in each of these ranges. Source 203may comprise one or more of an incandescent lamp, a gas discharge lamp(e.g., Halogen lamp, Xenon lamp, Argon lamp, Krypton lamp, etc.), alight emitting diode (LED), a white light LED, an organic LED (OLED), alaser (e.g., chemical laser, excimer laser, semiconductor laser, solidstate laser, Helium Neon laser, Argon laser, dye laser, diode laser,diode pumped laser, fiber laser, pulsed laser, continuous laser), or thelike.

Multiple capillary illumination for UV transmittance or absorptionmeasurements at the same UV wavelength has previously required the useof one or more UV sources such as a deuterium lamp, for example, incombination with a plurality of optical fibers located in front of aplurality of corresponding capillaries. There are various reasons forthis. A typical deuterium lamp used in the art for UV absorptionmeasurements in the CE context is very stable (low noise), but haslimited power. In a multiple capillary UV absorption measurement system,it is generally important to limit crosstalk between adjacentcapillaries. This may be achieved by using a small illumination spotsize in each capillary relative to the capillary's cross-sectional area.With a deuterium lamp UV source, this typically requires use of apinhole mask (or other mask) and/or fiber optics to achieve asufficiently compact system. However, much of the lamp's power is wastedin such systems and/or multiple lamps are needed to sufficientlyilluminate multiple capillaries. Also, because deuterium lamps have abroad-spectrum output of incoherent radiation, it is generally notpossible to focus a beam down to a dimension that is less than or equalto the capillary channel diameter.

Some preferred embodiments of the invention disclosed herein solve theabove problems by utilizing a UV laser or other UV source characterizedby high intensity or power, narrow wavelength band, and/or coherentemission. One embodiment uses a UV laser that is approximately 100 timesbrighter than a typical deuterium lamp and is able to provide beam thatmay be focused to a spot at which the beam diameter is less than orequal to the inner channel diameter of a capillary, yet with a smallnumerical aperture or divergence. Thus, the initial illumination powerof the UV laser source is greater than in prior systems using deuteriumlamps and has more favorable optical characteristic (e.g., small focusdiameter and divergence). Also, because a UV laser source can produce abeam with a much smaller diameter and numerical aperture than does adeuterium UV lamp, a sufficiently small illumination spot size on eachcapillary can be achieved using focusing rather than having to rely on,for example, a pinhole mask or fiber optic array. Thus, much less of thesource's illumination power is wasted and the sensitivity to variationsin transmittance/absorption of a capillary sample is improved, since allor most of the beam energy is transmitted through the inner capillarychannel. Thus, some embodiments of the invention implement optics thatdivide a single UV laser beam into multiple beamlets and that thendirect and focus respective beamlets onto respective capillaries with asufficiently small illumination spot size to avoid cross talk and withsufficient illumination power for obtaining usable transmittance orabsorption measurements. In some embodiments, other UV sources withthese favorable characteristics may be used instead of, or in additionto, a UV laser (e.g., a UV light emitting diode).

A challenge to using UV lasers in CE applications, rather than deuteriumlamps, is that lasers typically have a much higher source noise level.However, in some embodiments disclosed herein, this problem is addressedthrough the use of a reference capillary and a corresponding referencebeam. Additionally, as will be further described below, detectedelectromagnetic radiation (e.g., UV radiation) from the reference beammay be used by a digital signal processing unit to reduce or removenoise from detected radiation of the other beams (corresponding tocapillaries containing sample substances).

Tables 1-3 show optical characteristic of a UV laser having a Gaussianbeam shape. Such beams may be used, for example, with capillaries havinginner capillary channel diameters in the range of 50 micrometers to 200micrometers to achieve the above discussed advantages.

TABLE 1 Laser beam wavelength (nm) 220 280 Beam waist Diameter (um) 1010 Numerical Aperture 0.0140 0.0178 Divergence (at z = zR; radians)0.0280 0.0357 Divergence (at z = zR; degrees) 1.60 2.04

TABLE 2 Laser beam wavelength (nm) 220 280 Beam waist Diameter (um) 2020 Numerical Aperture 0.0070 0.0089 Divergence (at z = zR; radians)0.0140 0.0178 Divergence (at z = zR; degrees) 0.80 1.02

TABLE 3 Laser beam wavelength (nm) 220 280 Beam waist Diameter (um) 4040 Numerical Aperture 0.0035 0.0045 Divergence (at z = zR; radians)0.0070 0.0089 Divergence (at z = zR; degrees) 0.40 0.51

Instrument 1000 further comprises optical detectors 291, 292, 293, and294 and digital signal processing unit 290. Instrument 1000 may beadapted to either incorporate or be communicatively coupled with a userdevice 280, which comprises a processor, memory, storage, display,and/or user interface components (e.g. a display, keyboard and/or touchscreen, etc.) allowing a user to receive, use, and/or display datagenerated by instrument 1000 and, in some embodiments, control and/orconfigure aspects of instrument 1000. Digital signal processing (DSP)unit 290 processes signals from one or more of detectors 291-294 to,among other things, remove signal noise to help the instrument and userdevice obtain data usable for determining and displayingtransmittance/absorption and/or fluorescence measurements correspondingto substances processed by the instrument. It should be noted that, invarious embodiments, a DSP unit such as DSP 290 might be implemented inhardware, software, or a combination of hardware and software. Also, aDSP unit might be implemented on a connected user device and/or within adetection subsystem or other subsystem of the instrument itself.

Optical detectors 291, 292, 293, and 294 may comprise one or moreindividual photodetectors including, but not limited to, photodiodes,photomultiplier tubes, semiconductor detectors, multiple channel PMTs,or the like. Additionally, or alternatively, optical detectors 291, 292,293, and 294 may comprise an array sensor including an array of sensorsor pixels. The array sensor may comprise one or more of a complementarymetal-oxide-semiconductor sensor (CMOS), a charge-coupled device (CCD)sensor, a plurality of photodiodes detectors, a plurality ofphotomultiplier tubes, or the like. In certain embodiments, one or moreof optical detectors 291, 292, 293, and 294 may comprise a spectrometercomprising an array detector and a dispersive element such as areflection or transmission diffractive grating that spread incomingradiation into a spectrum across the detector array.

Sources 201-203, detectors 291-294, and DSP unit 290 are part of anoptical detection subsystem of instrument 1000. Other components of theoptical detection system include various optical components arranged toprovide various optical paths for beams travelling from sources 201-203to detectors 291-294. Those optical components and optical paths areillustrated and described below in the context of FIGS. 2-6 andaccompanying text, but are not separately shown in FIG. 1.

In summary, instrument 1000 operates as follows: A sample mixture orsolution containing various samples or sample molecules is prepared inor delivered into a sample source container 105. At least a portion ofthe sample mixture is introduced into one end of capillaries 101, forexample, at the cathode 103 using a pump or syringe (not separatelyshown) or by applying a charge or electric field to capillaries 101.With the sample solution loaded into the cathode end of a capillary 101,voltage supply 104 creates a voltage difference between cathode 103 andanode 102. The voltage difference causes negatively charged, dye-labeledsamples to move from sample source container 105 to sample destinationcontainer 106. Longer and/or less charged dye-labeled samples move at aslower rate than do shorter and/or higher charged dye-labeled samples,thereby creating some separation between samples of varying lengthsand/or charges. Beams originating from UV source 201, UV source 202,and/or visible light source 203 pass through a location within thecapillaries 101. Beams used for UV transmittance or absorptionmeasurements pass through capillaries 101 and are subsequently imagedonto detectors 291 and/or 292. Fluorescence resulting from a UV beamexciting substances in capillaries 101 is directed to detector 293.Fluorescence resulting from a visible light beam exciting substances incapillaries 101 is directed to detector 294. In certain embodiments, UVsources 201 and/or UV source 202 may be replaced or supplemented bysources including other wavelength bands, for example, visible light,infrared, or near-infrared bands, for the purpose of makingtransmittance or absorption measurements within those wavelength bands.

Signals are provided from one or more of detectors 291-294 to DSP unit290 for processing. Among other things, DSP 290 is configured to utilizesignals corresponding to a reference capillary 101 to reduce noise insignals corresponding to other capillaries 101 through which samples tobe measured pass. The output from DSP 290 is used by user device 280 orsimilar device to further process and display measurement resultscorresponding to measured samples.

FIG. 2 shows optical detection system 200 of instrument 1000 of FIG. 1in accordance with an embodiment of the invention. The illustratedcomponents provide multiple optical pathways from sources 201, 202, and203 to capillaries 101. In FIG. 2, a cross section of nine differentcapillaries 101 is shown. From the perspective of the illustrations inFIGS. 2-6, capillaries 101 extend longitudinally along a dimensionorthogonal to the illustration (i.e., into and out of the page).

The relevant optical pathways and optical components illustrated in FIG.2 will now be described in further detail, starting the pathway from UVsource 201 to detector 291.

Beam b1: UV Absorption Measurement

As illustrated in FIG. 2 and in FIG. 3, UV source 201 emits UV beam b1.Beam b1 passes through diffractive optical element 211, which operatesto split beam b1 into nine beamlets that may be collimated orapproximately collimated using a lens 212. Diffractive optical element211 may be optionally configured to otherwise condition the beamlets,for example, configured to change the convergence or divergence of oneor more of the beamlets from that of beam b1. The beamlets are reflectedby mirror 213 and passed through dichroic beam combiner 235. Dichroicbeam combiner 235 combines beamlets originating from beam b1 of UVsource 201, which operates at a first wavelength, and beamletsoriginating from beam b2 of UV source 202, which operates at a secondwavelength.

The beamlets then pass through capillaries 101. In the illustratedembodiment, eight of the capillaries contain samples to be measured andthe ninth capillary is used as a reference. The beamlets from beam b1passing through capillaries 101 are used to measure absorption and/ortransmittance, wherein a portion of each beamlet's power is absorbed bya corresponding sample-filled capillary 101 and another portiontransmits through the corresponding capillary 101. In certainembodiments, a smaller portion of a reference beamlet's power isabsorbed by a reference capillary 101 than through some or all of theremaining capillaries. The transmitted beamlets are focused by objectivelens 214 and reflected by dichroic mirror 215 which reflects UVradiation and allows visible light to pass through it. In this way, thebeamlets intersect one another and then diverge as they continue topropagate toward a mirror 216, while divergence of each beamletindividually may be decreased by lens 214. The UV beamlets then passthrough dichroic mirror 239, which reflects fluorescent light resultingfrom excitation of the substances in capillaries 101 by beam b2 (asseparately described further below). At dichroic mirror 229, the UVbeamlets are separated by wavelength such that beamlets originating frombeam b2 of UV source 202 are reflected and beamlets originating frombeam b1 of UV source 201 pass through to mirror 216. Mirror 216 reflectsthe beamlets from b1 and directs them to imaging lens 271 which imagesthem onto detector 291. In certain embodiments, a plurality of opticalelements (not shown) are located between mirror 216 and detector 291that each modify a respective one of the beamlets from b1.

Beam b2: Multiple Operational Modes

UV source 202 emits UV beam b2. In the illustrated embodiment, aspreviously described, UV source 202 operates at a different wavelengththan does UV source 201. The illustrated optical arrangement allowsoptical detection system 200 to utilize multiple operating modes withrespect to use of UV beam b2. In a first mode, UV beam b2 is utilizedentirely for absorption measurements of samples in capillaries 101. In asecond mode, UV beam b2 is utilized entirely for exciting fluorescencein samples in capillaries 101 and instrument 1000 then detects thatfluorescence. In a third mode, UV beam b2 is divided in manner thatallows a first portion of the beam to be used for absorptionmeasurements and a second portion of the beam to be used, substantiallysimultaneously, for exciting fluorescence. In some embodiments, insteadof using UV source 202 to make absorption measurements in capillaries101, optical detection system 200 further comprises a separate source(e.g., UV source) for making absorption measurements. In suchembodiments, optical elements 231 and 232 are not needed.

It should be noted that, in some embodiments, the disclosed system canbe configured to switch from one mode to another between sample runs.Thus, a first sample run could be conducted with the instrumentconfigured to implement the first mode referenced above, a second samplerun could be conducted with the instrument configured to implement thesecond mode, and a third sample run could be conducted with theinstrument configured to implement the third mode. In other embodiments,only the first or second mode could be implemented, but not the thirdmode. Also, in some embodiments implementing the third mode, theproportion of the original beam that is used for exciting fluorescenceversus absorption measurements can be adjusted between sample runs. Aswill be appreciated by those skilled in the art, enablingreconfigurability of the instrument to operate in one mode versusanother and/or to adjust the relative portion of beam b2's powerallocated to absorption measurements versus fluorescence excitation, canbe accomplished by, for example, using half wave plates in which theamount of polarization rotation applied by the half wave plate isadjustable.

Beam b2: UV Absorption Measurement

As illustrated in FIG. 2 and in FIG. 4, in the first mode, beam b2passes through half wave plate 221, polarizing beam splitter 222, andhalf wave plate 223 and is then reflected downward by polarizing beamsplitter 231. The beam is labelled as beam b2-A in FIG. 2 after beingreflected by polarizing beam splitter 231 simply to refer to the factthat the portion of beam b2 that is reflected by beam splitter 231 isused for absorption measurement. In the first mode, half wave plate 221,polarizing beam splitter 222, half wave plate 223, and polarizing beamsplitter 223 are configured such that all or substantially all of beamb2's energy is present in beam b2-A.

Beam b2-A is reflected by mirror 232 and passes through diffractiveoptical element 233, which operates to split beam b2-A into ninebeamlets that may be collimated or approximately collimated using a lens234. Diffractive optical element 233 may be optionally configured tootherwise condition the beamlets, for example, configured to change theconvergence or divergence of one or more of the beamlets from that ofbeam b1. The beamlets are redirected by dichroic beam combiner 235 tocombine with beamlets originating from beam b1 (as described above) andpass through capillaries 101. The beamlets from beam b2 passing throughcapillaries 101 are used to measure absorption at a different wavelengththan measured by those from beam b1.

As previously described, a portion of each beamlet's power is absorbedby a corresponding sample-filled capillary 101 and another portiontransmits through the corresponding capillary 101. In certainembodiments, a smaller portion of a reference beamlet's power isabsorbed by a reference capillary 101 than through some or all of theremaining capillaries. The transmitted beamlets are focused by objectivelens 214 and reflected by dichroic mirror 215. In this way, the beamletsintersect one another and then diverge as they continue to propagatetoward a mirror 216, while divergence of each beamlet individually maybe decreased by lens 214. The UV beamlets then pass through dichroicmirror 239. As previously described, at dichroic mirror 229, the UVbeamlets are separated by wavelength such that beamlets originating frombeam b2 of UV source 202 are reflected. Dichroic mirror 229 directs thebeamlets having beam b2's wavelength to imaging lens 272 which imagesthem onto detector 292. In certain embodiments, a plurality of opticalelements (not shown) are located between mirror 229 and detector 292that each modify a respective one of the beamlets from b2.

Beam b2: UV Fluorescence Measurement

As illustrated in FIG. 2 and in FIG. 5, in the second mode, half waveplate 221 and polarizing beam splitter 222 are configured to split beamb2 into two beams: b2-R and b2-L. In one embodiment, beam b2 is splitevenly into beams b2-R and b2-L. In other embodiments, the splittingratio can be adjusted to implement a non-even split.

Beam b2-R is reflected by mirror 226 through half wave plate 251 and isthen reflected by mirrors 227 and 228 before passing through dichroicmirror 247, and pinhole 238. Lens 248 then focuses the beam onto or nearcapillaries 101 and the beam propagates through capillaries 101 in afirst direction (right to left from the standpoint of the illustrationsof FIG. 2-6).

Beam b2-L passes through half wave plate 223, polarizing beam splitter231, half wave plate 224, dichroic mirror 244, and pinhole 236. Lens 225then focuses beam b2-L onto or near capillaries 101 and the beampropagates through capillaries 101 in a second direction, left to rightfrom perspective of the illustration, opposite to that of the directionof b2-R. Splitting beam b2 into beam portions b2-L and b2-R andpropagating each beam portion through the array of capillaries 101 inopposite direction allows more even excitation energy to be providedacross the array of capillaries 101.

Fluorescence resulting from excitation of substances in each of thecapillaries 101 by beams b2-L and b2-R is collected and collimated byobjective lens 214. The collected fluorescence emission from eachcapillary 101 is then reflected by dichroic mirrors 215 and 239 toimaging lens 273. Imaging lens 273 images the fluorescence beams fromeach capillary 101 onto detector 293.

The detection system 200 may include a grating 283 on the optical pathbetween dichroic mirror 239 and imaging lens 273 (alternatively, grating283 may be located between lens 273 and detector 293). For many usefulapplications, the samples of interest will have native fluorescence inresponse to excitation by a UV beam that can be detected within a singlenarrow wavelength range. In such applications, a grating such as grating283 will not be necessary. However, if the particular applicationbenefits from detecting UV fluorescence in two or more differentwavelength ranges, then grating 283 may be used to spread the beam overdetector 293 based on wavelength. For example, grating 283 may be usefulin applications that benefit from the ability to detect the presencedifferent UV fluorescent labels on different sample fragments.

Beam b2: Simultaneous Absorption and Fluorescence

In a third mode, beam b2 is used for both absorption and fluorescencemeasurements substantially simultaneously. In this mode, half wave plate221 and polarizing beam splitter 222 are configured to split beam b2 andpass a portion of through polarizing beam splitter 222 and to reflectanother portion from polarizing beam splitter 222 to mirror 226 as beamb2-R. Beam b2-R then propagates in the manner described above inreference to the second mode. The portion of beam b2 that passes throughpolarizing beam splitter 222 passes through half wave plate 223 and isthen further split at polarizing beam splitter 231 into two portions,b2-A and b2-L, based on the configuration of half wave plate 223. Beamb2-A propagates as described above in the context of the first mode(absorption). Beam b2-L propagates as described above in the context ofthe second beam b2 mode (fluorescent excitation).

In this third mode, beam b2's power is divided between multiple modes.Therefore, the portion of b2's power used for absorption andfluorescence excitation simultaneously is less than it is when thesystem is configured as described above to be used either entirely forone or the other, i.e., either entirely for the first mode (absorptionmeasurement) or entirely for the second mode (fluorescence measurement).

Beam b3: Visible Fluorescence

As illustrated in FIG. 2 and in FIG. 6, visible light source 203 emitsvisible light beam b3. Half wave plate 241 and polarizing beam splitter242 are configured to split beam b3 into two beams: b3-R and b3-L. Inone embodiment, beam b2 is split evenly into beams b2-R and b2-L. Inother embodiments, the splitting ratio can be adjusted to implement anon-even split.

Beam b3-R passes through half wave plate 245 and is reflected by mirror246 and dichroic mirror 247. Dichroic mirror reflects beam b3-R throughpinhole 238 to lens 248. Lens 248 then focuses the beam onto or nearcapillaries 101 and the beam propagates through capillaries 101 in afirst direction (right to left from the standpoint of the illustrationsof FIG. 2-6). Beam b3-L passes through half wave plate 243 and isreflected by dichroic mirror 244 through pinhole 236 to Lens 225. Lens225 then focuses the beam onto or near capillaries 101 and the beampropagates through capillaries 101 in a second direction, left to rightfrom perspective of the illustration, opposite to that of the directionof b3-R. Splitting beam b3 into beam portions b3-L and b3-R andpropagating each beam portion through the array of capillaries 101 inopposite direction allows excitation energy to be provided across thearray of capillaries 101 more evenly.

Fluorescence resulting from excitation of substances in capillaries 101by beams b3-L and b3-R is collected and collimated by objective lens214. It then passes through dichroic mirror 214 and transmission gratingto imaging lens 274. Transmission grating 284 spreads the spectrum ofvisible beams across detector 294 and imaging lens 274 images the beamsonto detector 294.

For fluorescent excitation beams originating from beams b2 (UV) and b3(visible), pinholes (or beam masks) 236 and 238 can be used to block,respectively, the right-to-left propagating beams (b2-R and b3-R) andleft-to-right propagating beams (b2-L and b3-L), as well as any backreflection from the capillary array resulting from those beams, frompropagating back to sources 202 and 203. Blocking of thecounter-propagating beams and back reflections by pinholes 236, 238 maybe enhanced by use of an offset angle in the forward propagating beams.

Half wave plates 224, 251, 243, and 245 can be used to rotatepolarization of beams b2-L (plate 224), b2-R (plate 251), b3-L (plate243), and b3-R (plate 245). The polarization rotations imparted byplates 224 and 251 (on UV beams b2-L and b2-R) can be used to controlRaman background emission intensity and/or to reduce laser beam backreflection. The polarization rotations imparted by plates 243 and 245(on visible light beams b3-L and b3-R) can be used for back groundcontrolling and/or reducing laser beam back reflection.

Dichroic mirrors 244 and 247 couple UV and visible light beams used forexciting fluorescence of substances in capillaries 101. Specifically,dichroic mirror 244 coupled UV beam b2-L and visible light beam b3-L anddichroic mirror 247 couples UV beam b2-R and visible light beam b3-R.

Various Feature Combinations

The illustrated embodiment of optical detection system embodies variousdifferent combinations of features. These various combinations, alone ortogether, each form potentially distinct embodiments and the use of somecombinations do not necessarily require use of the other combinations.For example:

In one aspect, optical detection system 200 provides optical pathwaysallowing a single UV source to be used for one or both of absorption andfluorescence measurements. In another aspect, the single UV source canbe used for both types of measurements simultaneously.

In another aspect, optical detection system 200 provides opticalpathways allowing two UV sources at different wavelengths to be used forabsorption measurements. In another aspect, at least some of the opticalcomponents along the pathways corresponding to UV absorptionmeasurements relying on each source are shared.

In another aspect, at least some optical components along a pathway forexciting fluorescence by a UV beam and along a pathway for excitingfluorescence by a visible light beam are shared and at least somecomponents along pathways for collecting and measuring fluorescence ofsubstances in capillaries excited by those beams are shared.

In a fully combined aspect, optical components are configured andarranged in optical detection system 200 to do the following: Measure UVabsorption of substances in an array of capillaries using two UV sourcesoperating a different wavelengths; excite and measure fluorescence ofsubstances in the array of capillaries using one of the two UV sources;and excite and measure fluorescence of substances in the array ofcapillaries using a visible light source. In another aspect, one or moreof the two UV sources and/or the visible light source are configured toprovide a point source, for example, a laser and one or more opticalelement to produce a point source. In a related aspect, reference beamsand a reference capillary are used to generate a reference signal foruse in removing noise from measurement signals corresponding to theother capillaries.

FIG. 3 illustrates, with some additional detail, the portion of opticaldetection system 200 that utilizes beam b1 for UV absorptionmeasurements. Elements illustrated in FIG. 2 and FIG. 3 that have thesame reference number are the same and will not necessarily be furtherdescribed here if they have already been described above in the contextof FIG. 2, except to the extent that their description is useful forexplaining the additional details illustrated in FIG. 3.

FIG. 3 illustrates an exploded view of capillaries 101. The illustratedembodiment has nine capillaries including capillaries 101-1, 101-2,101-3, 101-4, 101-5, 101-6, 101-7, 101-8, and 101-ref. Capillary 101-refis used as a reference and does not contain biological samples. Theother eight capillaries are used to convey sample solutions that containsamples to be analyzed. As previously described, diffractive opticalelement 211 operates to divide beam b1 into nine beamlets. Lens 212operates to collimate or approximately collimate the beamlets relativeto each other (i.e., direct them substantially parallel to each other)and also includes lenslets that operate to focus each beamletindividually. As shown in FIG. 3, diffractive optical element 211 and/orlens 212 may be configured to focus respective beamlets 31, 32, 33, 34,25, 36, 37, 38, and 3ref onto or near respective capillary coresresulting in respective UV spots s31, s32, s33, s34, s35, s36, s37, s38,and s3ref. In one embodiment, each respective beamlet is focused suchthat its diameter decreases from 1 millimeter at lens 212 toapproximately 10 microns at a respective capillary core. In otherembodiments, other optical focusing powers can be used. The desired spotsize or beam diameter at capillaries 101 (and hence the needed focusingpower) will depend in part on the diameter of capillaries used for aparticular implementation. In certain embodiments, one or more opticalelements (not shown), such as one or more lenslets or diffractiveoptical elements, may be placed between source 201 and capillaries 101to individually control the focus of one or more corresponding beamlets31, 32, 33, 34, 25, 36, 37, 38, and/or 3ref.

Additionally or alternatively, one or more additional optical elements(not shown) may be placed at or near one or more of detectors 291, 292,293, and/or 294 to individually control the focus of one or morecorresponding beamlets 31, 32, 33, 34, 25, 36, 37, 38, and/or 3ref, Incertain embodiments, one or more of beamlets 31, 32, 33, 34, 25, 36, 37,38, and/or 3ref preferably come to focus or have a minimum diameter ator near capillaries 101.

FIG. 3 also illustrates an exploded view of a portion of detector 291.The optical components between the array of capillaries 101 and detector291 serve to direct images of respective UV spots s31, s32, s33, s34,s35, s36, s37, s38, and s3ref onto detector 291 as respective imagespots. To avoid overcomplicating the drawing, only images spots is31,is35, and is3ref are separately labelled. These are images of,respectively, UV spots s31, s35, and s3ref. Beamlet 3ref, and itscorresponding UV spot s3ref on capillary 101-refs core, and image spotis3ref on detector 291 provide a reference signal that, in theillustrated embodiment, is used to remove noise from signalscorresponding to the images of capillary core UV spots s31-s38 ondetector 291, resulting from beamlets 31-38.

FIG. 4 illustrates, with some additional detail, the portion of opticaldetection system 200 that utilizes beam b2 for UV absorptionmeasurements. Elements illustrated in FIG. 2 and FIG. 4 that have thesame reference number are the same and will not necessarily be furtherdescribed here if they have already been described above in the contextof FIG. 2, except to the extent that their description is useful forexplaining the additional details illustrated in FIG. 4.

As previously described, diffractive optical element 233 and lens 234operate to divide beam b2 into nine beamlets. Lens 234 operates in asimilar manner to that described above for lens 212 of FIG. 3. As shownin FIG. 4's exploded view of capillaries 101, respective beamlets 41,42, 43, 44, 45, 46, 47, 48, and 4ref are focused onto respectivecapillary cores resulting in respective UV spots s41, s42, s43, s44,s45, s46, s47, s48, and s4ref.

FIG. 4 also illustrates an exploded view of a portion of detector 292.The optical components between the array of capillaries 101 and detector292 serve to direct images of respective UV spots s41, s42, s43, s44,s45, s46, s47, s48, and s4ref onto detector 292 as respective imagespots. To avoid overcomplicating the drawing, only images spots is41,is45, and is4ref are separately labelled. These are images of,respectively, UV spots s41, s45, and s4ref. Beamlet 4ref, and itscorresponding UV spot s4ref on capillary 4ref s core, and image spotis4ref on detector 292 provide a reference signal that, in theillustrated embodiment, is used to remove noise from signalscorresponding to the images of capillary core UV spots s41-s48 ondetector 292, resulting from beamlets 41-48.

It is understood that when the system of the illustrated embodiment isoperated to measure absorption using both beams b1 and b2, theillustrated beamlets in FIG. 3 and FIG. 4 are in fact respectivelycombined (e.g., beamlet 31 and 41 are combined) in the portion of theoptical path between dichroic beam combiner 235 and dichroic mirror 239,including when transmitted through capillaries 101. In such case, thereferences in FIG. 3 and FIG. 4 to, for example beamlet 31 and 41, infact refer to the relevant portions of a combined beamlet, the portionscorresponding to, respectively, UV radiation at a first wavelengthprovided by source 201 (e.g., beamlet 31) and UV radiation at adifferent wavelength provided by source 202 (e.g., beamlet 41).

FIG. 5 illustrates, with some additional detail, the portion of opticaldetection system 200 that utilizes beam b2 for UV fluorescencemeasurements. Elements illustrated in FIG. 2 and FIG. 5 that have thesame reference number are the same and will not necessarily be furtherdescribed here if they have already been described above in the contextof FIG. 2, except to the extent that their description is useful forexplaining the additional details illustrated in FIG. 5.

As previously described, a portion of beam b2 that is not utilized forabsorption measurements is split into beams b2-L and b2-R to illuminatecapillaries 101 from opposite directions (left to right and right toleft from the perspective of FIG. 5). As shown in FIG. 5's exploded viewof capillaries 101, this illumination results in fluorescent emissioncorresponding to UV spots s51, s52, s53, s54, s55, s56, s57, s58, ands5ref.

FIG. 5 also illustrates an exploded view of a portion of detector 293.The optical components between the array of capillaries 101 and detector293 serve to direct images of respective UV spots s51, s52, s53, s54,s55, s56, s57, s58, and s5ref onto detector 293 as respective imagespots. To avoid overcomplicating the drawing, only images spots is51,is54, is58, and is5ref are separately labelled. These are images of,respectively, UV spots s51, s54, s58, and s5ref. UV spot s5ref, andimage spot is5ref on detector 293 provide a reference signal that, inthe illustrated embodiment, is used to remove noise from signalscorresponding to the images of fluorescent emission UV spots s51-s58 ondetector 293.

FIG. 6 illustrates, with some additional detail, the portion of opticaldetection system 200 that utilizes beam b3 for visible lightfluorescence measurements. Elements illustrated in FIG. 2 and FIG. 6that have the same reference number are the same and will notnecessarily be further described here if they have already beendescribed above in the context of FIG. 2, except to the extent thattheir description is useful for explaining the additional detailsillustrated in FIG. 6.

As previously described, beam b3 is split into beams b3-L and b3-R toilluminate capillaries 101 from opposite directions (left to right andright to left from the perspective of FIG. 6). As shown in FIG. 6'sexploded view of capillaries 101, this illumination results influorescent emission corresponding to spots s61, s62, s63, s64, s65,s66, s67, s68, and s6ref.

FIG. 6 also illustrates an exploded view of a portion of detector 294.The optical components between the array of capillaries 101 and detector294 serve to direct images of respective spots s61, s62, s63, s64, s65,s66, s67, s68, and s6ref onto detector 294 as respective image spots. Toavoid overcomplicating the drawing, only images spots is61, is64, is68,and is6ref are separately labelled. These are images of, respectively,spots s61, s64, s68, and s6ref. Spot s6ref, and image spot is6ref ondetector 294 provide a reference signal that, in the illustratedembodiment, is used to remove noise from signals corresponding to theimages of fluorescent emission spots s61-s68 on detector 294.

It is understood that when the system of the illustrated embodiment isoperated to measure fluorescence resulting from illumination by bothbeams originating from UV beam b2 and beams originating from visiblebeam b3, beams b2-L and b3-L are combined at dichroic mirror 244 andbeams b2-R and b3-R are combined at dichroic mirror 247. Thus, forexample, the references in FIG. 5 and FIG. 6 to beam b2-L and b3-L (orbeam b3-L and b3-R) in fact refer to the relevant portions of a combinedbeam, the portions corresponding to, respectively, UV radiationoriginating from source 202 and visible light originating from source203. Also, fluorescence emissions from capillaries 101 combine radiationat different wavelengths which is then separated at UV-visible lightdichroic mirror 215 before being imaged onto, respectively, detectors293 and 294.

FIG. 7 is a block diagram illustrating signals output from detectors291, 292, 293, 294 to DSP unit 290 and reduced noise signals output byDSP unit 290. As will be appreciated, the separate lines shown from thedetectors to DSP unit 290 and shown as output from DSP unit 290 do notnecessarily represent distinct hardware connections between (and outputsfrom) the illustrated elements. Rather, they simply represent distinctsignal channels. In some embodiments, these separate signal channelsmight be implemented with physically separate connections; however, inother embodiments, they are implemented as separate signal channelsconveyed over the same physical conduit.

Each detector outputs nine signals to DSP unit 290, i.e., onecorresponding to each capillary measurement including measurement ofeight capillaries comprising sample solutions and one referencecapillary without any sample-filled solution. Detector 291 outputs toDSP 290 signals 71-1, 71-2, 71-3, 71-4, 71-5, 71-6,71-7, 71-8, and71-ref, corresponding to first wavelength UV absorption measurements of,respectively, capillaries 101-1, 101-2, 101-3, 101-4, 101-5, 101-6,101-7, 101-8, and 101-ref. Signals 71-1 to 78-8 will include noiserelated to source 201, noise related to sample solutions, and noiserelated to the respective capillaries. Signal 71-ref will contain thenoise related to source 201 and capillary 101-ref, but it will notcontain noise related to samples. DPS unit 290 removes noise related tothe source 201 and the capillaries from signals 71-1 to 71-8 bycomparing them to reference signal 71-ref using, for example, a crosscorrelation technique employing methods such as Weiner filtering, leastsquares filtering, and/or other techniques to obtain DSP output signals81-1, 81-2, 81-3, 81-4, 81-5, 81-6, 81-7. and 81-8 which havesubstantially reduced source and capillary related noise relative tosignals 71-1 to 71-8.

Detector 292 outputs to DSP 290 signals 72-1, 72-2, 72-3, 72-4, 72-5,72-6,72-7, 72-8, and 72-ref, corresponding to second wavelength UVabsorption measurements of, respectively, capillaries 101-1, 101-2,101-3, 101-4, 101-5, 101-6, 101-7, 101-8, and 101-ref. Signals 72-1 to72-8 will include noise related to source 202, noise related to samplesolutions, and noise related to the respective capillaries. Signal72-ref will contain the noise related to source 202 and capillary101-ref, but it will not contain noise related to samples. DPS unit 290removes noise related to the source and the capillaries from signals72-1 to 72-8 by comparing them to reference signal 72-ref using, forexample, the previously described techniques for removing signal noise.DSP 290 outputs signals 82-1, 82-2, 82-3, 82-4, 82-5, 82-6, 82-7. and82-8 which have substantially reduced source and capillary related noiserelative to signals 72-1 to 72-8.

Detector 293 outputs to DSP 290 signals 73-1, 73-2, 73-3, 73-4, 73-5,73-6,73-7, 73-8, and 73-ref, corresponding to UV fluorescencemeasurements of, respectively, capillaries 101-1, 101-2, 101-3, 101-4,101-5, 101-6, 101-7, 101-8, and 101-ref. Signals 73-1 to 73-8 willinclude noise related to source 202, noise related to sample solutions,and noise related to the respective capillaries. Signal 73-ref willcontain the noise related to source 202 and capillary 101-ref, but itwill not contain noise related to samples. DPS unit 290 removes noiserelated to the source and the capillaries from signals 73-1 to 73-8 bycomparing them to reference signal 73-ref using, for example, thepreviously described techniques for removing signal noise. DSP 290outputs signals 83-1, 83-2, 83-3, 83-4, 83-5, 83-6, 83-7. and 83-8 whichhave substantially reduced source and capillary related noise relativeto signals 73-1 to 73-8.

Detector 294 outputs to DSP 290 signals 74-1, 74-2, 74-3, 74-4, 74-5,74-6,74-7, 74-8, and 74-ref, corresponding to UV fluorescencemeasurements of, respectively, capillaries 101-1, 101-2, 101-3, 101-4,101-5, 101-6, 101-7, 101-8, and 101-ref. Signals 74-1 to 74-8 willinclude noise related to source 202, noise related to sample solutions,and noise related to the respective capillaries. Signal 74-ref willcontain the noise related to source 202 and capillary 101-ref, but itwill not contain noise related to samples. DPS unit 290 removes noiserelated to the source and the capillaries from signals 74-1 to 74-8 bycomparing them to reference signal 74-ref using, for example, thepreviously described techniques for removing signal noise. DSP 290outputs signals 84-1, 84-2, 84-3, 84-4, 84-5, 84-6, 84-7. and 84-8 whichhave substantially reduced source and capillary related noise relativeto signals 74-1 to 74-8.

DSP 290 can be implemented as processing logic in specificallyconfigured hardware for example, in a Field Programmable Gate Array(FPGA) programmed for the relevant processing logic, in custom hardware,for example, in an Application Specific Integrated Circuit (ASIC),and/or in software executing on a special or general purpose processor(for example, on a processor of user device 280, or on a processorlocated elsewhere in instrument 1000).

While the present invention has been particularly described with respectto the illustrated embodiments, it will be appreciated that variousalterations, modifications and adaptations may be made based on thepresent disclosure and are intended to be within the scope of thepresent invention.

Some examples of the many alternatives to the disclosed embodiments thatcould be implemented consistent with the spirit and scope of variousaspects of the invention include, but are not limited, to the following:In some alternative embodiments, reflection rather than transmissionoptics (e.g., parabolic mirrors rather than lenses) can be used todirect the relevant beams onto the capillaries. In some embodiments,reflection rather than transmission optics could be used to direct therelevant beams onto the relevant detectors. In some alternativeembodiments, optical fibers can be used to direct the relevantelectromagnetic radiation onto the capillaries and/or to direct therelevant electromagnetic radiation onto the relevant detectors. In suchoptical fiber alternatives, many of the optical components illustratedin the FIGS. 2-6 would not be needed. In some embodiments, opticalfibers could be used for the detection pathways (to direct light fromthe capillaries to the detectors) but not necessarily used for theillumination pathways (directing electromagnetic radiation from thesource(s) to the capillaries).

In the illustrated embodiments, both transmittance/absorptionmeasurements and fluorescent measurements are conducted based onilluminating the same window of a given capillary of the array. In otherwords, the same area of a capillary is targeted for illumination relatedto transmittance/absorption measurements and for illumination related tofluorescence measurements. However, in some alternative, separatewindows could be used. For example, illumination for UV absorptionmeasurements could occur at a first area of the capillary andillumination for fluorescence measurements could occur at a second area,longitudinally distant from the first area. In such embodiments,distinct optical paths would be implemented for each window and some ofthe separation optics of the embodiments illustrated in FIGS. 2-6 wouldnot necessarily be needed.

These and other variations will be understood to be within the scope ofthe invention's potential embodiments.

While the invention has been described in connection with what arepresently considered to be the most practical and preferred embodiments,it is to be understood that the present invention is not limited to thedisclosed embodiments but, on the contrary, is intended to cover variousmodifications and equivalent arrangements included within the scope ofthe underlying principles of the invention as described by the variousembodiments reference above and below.

1. An optical detection system for a capillary electrophoresisinstrument comprising: an ultraviolet (UV) source; and an absorptionmeasurement optical path comprising a first plurality of opticalelements arranged to obtain a plurality of respective UV beamlets from aUV beam emitted by the UV source and to direct the respective UVbeamlets transversely through respective capillaries of a plurality ofcapillaries and to an absorption detector positioned to detectrespective signals for use in obtaining respective UV absorptionmeasurements corresponding to the respective capillaries.
 2. The opticaldetection system of claim 1 further comprising: a fluorescenceexcitation optical path comprising a second plurality of opticalelements arranged to direct the UV beam transversely though theplurality of capillaries and to direct respective fluorescence signalsfrom the respective capillaries of the plurality of capillaries to afluorescence detector positioned to detect the respective signals foruse in obtaining respective fluorescence measurements corresponding tothe respective capillaries.
 3. The optical detection system of claim 2wherein the second plurality of optical elements comprises at least someof the first plurality of optical elements.
 4. The optical detectionsystem of claim 2 wherein one or more optical elements of the firstplurality of optical elements and the second plurality of opticalelements are configurable to direct respective portions of the UV beamthrough the absorption measurement optical path and through thefluorescence measurement optical path substantially simultaneously. 5.The optical detection system of claim 2 wherein one or more opticalelements of the first plurality of optical elements and the secondplurality of optical elements are configurable to reconfigure theoptical detection system between a first mode and a second mode, thefirst mode characterized by a configuration of the system in which theUV beam is directed on the absorption measurement optical path and thesecond mode characterized by a configuration of the system in which theUV beam is directed on the fluorescence measurement optical path.
 6. Theoptical detection system of claim 1 wherein the UV source is a first UVsource that operates at a first wavelength, the UV beam is a first UVbeam, and the absorption measurement optical path is a first absorptionmeasurement optical path, the optical detection system furthercomprising: a second UV source that operates at a second wavelength; anda second absorption measurement optical path comprising a thirdplurality of optical elements arranged to obtain a plurality ofrespective UV beamlets from a UV beam emitted by the second UV sourceand to direct the respective UV beamlets transversely through respectivecapillaries of a plurality of capillaries and to an absorption detectorpositioned to detect respective signals for use in obtaining respectiveUV absorption measurements corresponding to the respective capillaries.7. The optical detection system of claim 1 further comprising: a visiblelight source; a fluorescence excitation optical path comprising a thirdplurality of optical elements arranged to direct a fluorescenceexcitation light beam from the visible light source transversely thoughthe plurality of capillaries and to direct respective fluorescencesignals from the respective capillaries of the plurality of capillariesto a visible light fluorescence detector positioned to detect therespective signals for use in obtaining respective fluorescencemeasurements corresponding to the respective capillaries.
 8. The opticaldetection system of claim 1 wherein the UV source is a point source. 9.The optical detection system of claim 8 wherein one of the respectivecapillaries is designated as a reference capillary, the opticaldetection system further comprising: a digital signal processing unitconfigured to use signals corresponding to the reference capillary toremove UV source and capillary signal noise from signals correspondingto other capillaries of the respective capillaries wherein the othercapillaries are designated to carry samples.
 10. The optical detectionsystem of claim 1 wherein the first plurality of optical elementscomprise a diffractive optical element used to obtain the respective UVbeamlets from the UV beam.
 11. An optical detection system for acapillary electrophoresis instrument comprising: a first ultraviolet(UV) source that operates at a first wavelength; a first absorptionmeasurement optical path comprising a first plurality of opticalelements arranged to obtain a plurality of first respective UV beamletsfrom a UV beam emitted by the first UV source and to direct therespective UV beamlets transversely through respective capillaries of aplurality of capillaries and to an absorption detector positioned todetect respective signals for use in obtaining respective UV absorptionmeasurements corresponding to the respective capillaries; a second UVsource that operates at a second wavelength; and a second absorptionmeasurement optical path comprising a second plurality of opticalelements arranged to obtain a plurality of second respective UV beamletsfrom a UV beam emitted by the second UV source and to direct the secondrespective UV beamlets transversely through respective capillaries ofthe plurality of capillaries and to an absorption detector positioned todetect respective signals for use in obtaining respective UV absorptionmeasurements corresponding to the respective capillaries.
 12. Theoptical detection system of claim 11 wherein the second plurality ofoptical elements comprises at least some of the first plurality ofoptical elements.
 13. The optical detection system of claim 11 furthercomprising: a fluorescence excitation optical path comprising a thirdplurality of optical elements arranged to direct a UV beam originatedfrom the first UV source transversely though the plurality ofcapillaries and to direct respective fluorescence signals from therespective capillaries of the plurality of capillaries to a fluorescencedetector positioned to detect the respective signals for use inobtaining respective fluorescence measurements corresponding to therespective capillaries.
 14. The optical detection system of claim 13wherein the third plurality of optical elements comprises at least someof the first plurality of optical elements.
 15. The optical detectionsystem of claim 11 further comprising: a visible light source; afluorescence excitation optical path comprising a fourth plurality ofoptical elements arranged to direct a fluorescence excitation light beamfrom the visible light source transversely though the plurality ofcapillaries and to direct respective fluorescence signals from therespective capillaries of the plurality of capillaries to a visiblelight fluorescence detector positioned to detect the respective signalsfor use in obtaining respective fluorescence measurements correspondingto the respective capillaries.
 16. The optical detection system of claim15 wherein the fourth plurality of optical elements comprises at leastsome of the third plurality of optical elements.
 17. The opticaldetection system of claim 11 wherein the first UV source and the secondUV source are point sources.
 18. The optical detection system of claim17 wherein one of the respective capillaries is designated as areference capillary, the optical detection system further comprising: adigital signal processing unit configured to use signals correspondingto the reference capillary to remove UV source and capillary signalnoise from signals corresponding to other capillaries of the respectivecapillaries wherein the other capillaries are designated to carrysamples.
 19. The optical detection system of claim 11 wherein the firstplurality of optical elements comprises a diffractive optical elementused to obtain the first respective UV beamlets from the first UV beam.20. An optical detection system for a capillary electrophoresisinstrument comprising: an ultraviolet (UV) point source; an absorptionmeasurement optical path comprising a first plurality of opticalelements arranged to obtain a plurality of respective UV beamlets from aUV beam emitted by the UV point source and to direct the respective UVbeamlets transversely through respective capillaries of a plurality ofcapillaries and to an absorption detector positioned to detectrespective signals for use in obtaining respective UV absorptionmeasurements corresponding to the respective capillaries. 21-29.(canceled)